Chemical Conversion of Corticosteroids to 3α, 5α-Tetrahydro Derivatives. Synthesis of Allotetra-hydrocortisol Glucuronides and Allotetrahydrocortisone Glucuronides

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The synthesis of the 3- and 21-glucuronides of allotetrahydrocortisol (allo-THF) and allotetrahydrocortisone (allo-THE) is described. 5α-Dihydrocortisol (5) was prepared by selective hydrogenation of 21-acetoxy-3,11β, 17α-trihydroxy-3,5-pregnadien-20-one 3-ethyl ether (3), followed by acid hydrolysis and saponification. When 5α-dihydrocortisol 21-tetrahydropyranyl ether (6) was treated with potassium tri-sec-butylborohydride in tetrahydrofuran under mild conditions, regioselective and stereoselective reduction at C-3 took place to give allo-THF 21-tetrahydrophyranyl ether (7). This compound was converted into the 3- and 21-monoacetates of allo-THF and allo-THE, key intermediates. Introduction of the glucuronyl residue at C-3 or C-21 was carried out by means of the Koenigs-Knorr reaction. Prior to saponification yielding the 3-glucuronides (20,23), the alkali-sensitive ketol side chain at C-17 was protected as 20-semicarbazones.
公益社団法人日本薬学会の論文
1990-07-25